Molecular epidemiology of human cancer

A challenging goal of molecular epidemiology is to identify an individual's risk of cancer. Molecular epidemiology integrates molecular biology, in vi tro and in vivo laboratory models, biochemistry, and epidemiology to infer individual cancer risk. Molecular dosimetry of carcinogen exposure is an im portant facet of molecular epidemiology and cancer risk assessment. Carcino gen macromolecular adduct levels, cytogenetic alterations and somatic cell mutations can be measured to determine the biologically-effective doses of carcinogens. Molecular epidemiology also explores host cancer susceptibilit ies, such as carcinogen metabolism, DNA repair, and epigenetic and genetic alterations in tumor suppressor genes. p53 is a prototype tumor suppressor gene and is well suited for analysis of mutational spectrum in human cancer . The analyses of germline and somatic mutation spectra of the p53 tumor su ppressor gene provide important clues for cancer risk assessment in molecul ar epidemiology. For example, characteristic p53 mutation spectra have been associated with: dietary aflatoxin B-1 exposure and hepatocellular carcino ma; sunlight exposure and skin carcinoma; and cigarette smoking and lung ca ncer. The mutation spectrum also reveals those p53 mutants that provide cel ls with a selective clonal-expansion advantage during the multistep process of carcinogenesis. The p53 gene encodes a multifunctional protein involved in the cellular response to stress including DNA damage and hypoxia. Certa in p53 mutants lose tumor suppressor activity and gain oncogenic activity, which is one explanation for the commonality of p53 mutations in human canc er. Molecular epidemiological results can be evaluated for causation by inf erence of the Bradford-Hill criteria, i.e. strength of association (consist ency, specificity and temporality) and biological plausibility, which utili zes the 'weight of the evidence principle'. (C) 1998 Elsevier Science Irela nd Ltd. All rights reserved.